Cause of Type 1 Diabetes
Type 1 diabetes is primarily caused by cellular-mediated autoimmune destruction of pancreatic β-cells, resulting in absolute insulin deficiency. 1
Autoimmune Mechanism
The autoimmune destruction of pancreatic β-cells involves several key components:
Autoimmune markers: The presence of one or more autoantibodies defines type 1 diabetes, including:
- Islet cell autoantibodies
- Autoantibodies to GAD (GAD65)
- Autoantibodies to insulin
- Autoantibodies to tyrosine phosphatases IA-2 and IA-2b
- Autoantibodies to zinc transporter 8 (ZnT8) 1
Genetic factors: Type 1 diabetes has strong genetic associations:
Environmental triggers: Environmental factors play a role in triggering the autoimmune process, though these remain poorly defined 1
Disease Progression
The rate of β-cell destruction varies considerably among individuals:
- Rapid progression: Common in infants and children
- Slower progression: More typical in adults
- Variable presentation: Some patients (particularly children) present with diabetic ketoacidosis (DKA) as the first manifestation
- Gradual onset: Others initially have modest fasting hyperglycemia that can rapidly worsen with infection or stress 1
Approximately 40-50% of children with Type 1 diabetes present with diabetic ketoacidosis at diagnosis 2.
Epidemiology and Classification
- Type 1 diabetes accounts for only 5-10% of all diabetes cases 1
- Previously called "insulin-dependent diabetes" or "juvenile-onset diabetes"
- Can occur at any age, though commonly presents in childhood and adolescence
- Can develop even in the 8th and 9th decades of life 1
Idiopathic Type 1 Diabetes
A minority of type 1 diabetes cases have no known etiology:
- These patients have permanent insulinopenia and are prone to DKA
- No evidence of β-cell autoimmunity (negative for autoantibodies)
- Most common in individuals of African or Asian ancestry
- This form is strongly inherited but not HLA-associated
- Patients may have intermittent requirements for insulin replacement 1
Associated Conditions
Patients with type 1 diabetes are prone to other autoimmune disorders:
- Hashimoto thyroiditis
- Graves disease
- Addison disease
- Celiac disease
- Vitiligo
- Autoimmune hepatitis
- Myasthenia gravis
- Pernicious anemia 1
Diagnostic Considerations
Features most useful in identifying Type 1 diabetes include:
- Younger age at diagnosis
- Lower BMI
- Unintentional weight loss
- Ketoacidosis
- High glucose levels at presentation 2
When the diagnosis is unclear, testing for islet autoantibodies and C-peptide levels (after disease duration >3 years) can help distinguish between type 1 and type 2 diabetes 2.
It's important to note that misdiagnosis is common, occurring in up to 40% of adults with new-onset type 1 diabetes, highlighting the importance of careful diagnostic evaluation 2.